Brains Sweep Themselves Clean Of Toxins During Sleep

While the brain sleeps, it clears out harmful toxins, a process that may reduce the risk of Alzheimer's, researchers say.

During sleep, the flow of cerebrospinal fluid in the brain increases dramatically, washing away harmful waste proteins that build up between brain cells during waking hours, a study of mice found.

"It's like a dishwasher," says Dr. Maiken Nedergaard, a professor of neurosurgery at the University of Rochester and an author of the study in Science.

The results appear to offer the best explanation yet of why animals and people need sleep. If this proves to be true in humans as well, it could help explain a mysterious association between sleep disorders and brain diseases, including Alzheimer's.

Nedergaard and a team of scientists discovered the cleaning process while studying the brains of sleeping mice.

The scientists noticed that during sleep, the system that circulates cerebrospinal fluid through the brain and nervous system was "pumping fluid into the brain and removing fluid from the brain in a very rapid pace," Nedergaard says.

The team discovered that this increased flow was possible in part because when mice went to sleep, their brain cells actually shrank, making it easier for fluid to circulate. When an animal woke up, the brain cells enlarged again and the flow between cells slowed to a trickle. "It's almost like opening and closing a faucet," Nedergaard says. "It's that dramatic."

The process is important because what's getting washed away during sleep are waste proteins that are toxic to brain cells, Nedergaard says. This could explain why we don't think clearly after a sleepless night and why a prolonged lack of sleep can actually kill an animal or a person, she says.

So why doesn't the brain do this sort of housekeeping all the time? Nedergaard thinks it's because cleaning takes a lot of energy. "It's probably not possible for the brain to both clean itself and at the same time [be] aware of the surroundings and talk and move and so on," she says.

The brain-cleaning process has been observed in rats and baboons, but not yet in humans, Nedergaard says. Even so, it could offer a new way of understanding human brain diseases including Alzheimer's. That's because one of the waste products removed from the brain during sleep is beta amyloid, the substance that forms sticky plaques associated with the disease.

That's probably not a coincidence, Nedergaard says. "Isn't it interesting that Alzheimer's and all other diseases associated with dementia, they are linked to sleep disorders," she says.

Researchers who study Alzheimer's say Nedergaard's research could help explain a number of recent findings related to sleep. One of these involves how sleep affects levels of beta amyloid, says Randall Bateman, a professor of neurology Washington University in St. Louis who wasn't involved in the study.

"Beta amyloid concentrations continue to increase while a person is awake," Bateman says. "And then after people go to sleep that concentration of beta amyloid decreases. This report provides a beautiful mechanism by which this may be happening."

The report also offers a tantalizing hint of a new approach to Alzheimer's prevention, Bateman says. "It does raise the possibility that one might be able to actually control sleep in a way to improve the clearance of beta amyloid and help prevent amyloidosis that we think can lead to Alzheimer's disease."

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Transcript

ROBERT SIEGEL, HOST:

The question of why people and animals need sleep has bothered scientists for decades. And now, researchers think that they've found at least part of the answer. NPR's Jon Hamilton reports on a study that shows that during sleep, the brain flushes out toxins, including a substance linked to Alzheimer's disease.

JON HAMIILTON, BYLINE: From an evolutionary point of view, sleep seems like a bad idea. After all, when you're snoozing, it's easy for another creature to remove you from the gene pool. That's especially true if you're a small rodent, says the University of Rochester's Maiken Nedergaard.

DR. MAIKEN NEDERGAARD: For a animal like a mouse or rat, it's very dangerous to sleep because it's much more vulnerable for cats that would come and eat it.

JON HAMILTON, BYLINE: So sleep must have some really important survival function. To find out what that might be, Nedergaard led a team that studied the brains of sleeping mice. And the scientists noticed that during sleep, something odd was happening to the system that circulates cerebrospinal fluid through the brain and nervous system.

NEDERGAARD: It was pumping fluid into the brain and removing fluid from the brain in a very rapid pace.

HAMILTON: Nedergaard says the team realized this was possible in part because when mice went to sleep, their brain cells actually shrank, so it was easier for fluid to circulate. When an animal woke up, she says, the brain cells enlarged again and the flow between cells slowed to a trickle.

NEDERGAARD: It's almost like opening and closing a faucet. It's that dramatic.

HAMILTON: Nedergaard and her team had previously shown that the fluid was carrying away waste products that build up in the spaces between cells.

NEDERGAARD: It's like a dishwasher. It's floating by all the cells, which are the dishes, and washing them.

HAMILTON: That's important because what's getting washed away during sleep are waste proteins that are toxic to brain cells. Nedergaard says this process could explain why we don't think clearly after a sleepless night and why a prolonged lack of sleep can actually kill an animal or a person. But why doesn't the brain do this sort of housekeeping all the time? Nedergaard thinks it's because cleaning takes a lot of energy.

NEDERGAARD: It's probably not possible for the brain to both clean itself and at the same time being aware of the surroundings and talk and move and so on.

HAMILTON: And that would explain why animals have evolved to need sleep. Nedergaard says the cleaning process has been observed in rats and baboons but not yet in humans. Even so, it could offer a new way of understanding human brain diseases, including Alzheimer's. That's because one of the waste products removed from the brain during sleep is beta-amyloid, the substance that forms sticky plaques associated with Alzheimer's. Nedergaard says that's probably not a coincidence.

NEDERGAARD: Isn't it interesting that Alzheimer and all other diseases associated with dementia, they are linked to sleep disorders. So the patient would sleep less and less and they would not have deep sleep.

HAMILTON: Researchers who study Alzheimer's say Nedergaard's research could help explain a number of recent findings related to sleep. Randall Bateman of Washington University in St. Louis was part of a team that studied how sleep affects levels of that Alzheimer's protein, beta-amyloid.

DR. RANDALL BATEMAN: Beta-amyloid concentrations continue to increase while a person is awake. And then after people go to sleep, that concentration of beta-amyloid decreases. This report provides a beautiful mechanism by which this may be happening.

HAMILTON: Bateman says the report also offers a tantalizing hint of a new approach to Alzheimer's prevention.

BATEMAN: It does raise the possibility that one might be able to actually control sleep in a way to improve the clearance of beta-amyloid and help prevent amyloidosis that we think can lead to Alzheimer's disease.

HAMILTON: The new research appears in the journal Science. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.